Use of Palliative Care Among Commercially Insured Patients With Metastatic Cancer Between 2001 and 2016.

PURPOSE: Early palliative care, concomitant with disease-directed treatments, is recommended for all patients with advanced cancer. This study assesses population-level trends in palliative care use among a large cohort of commercially insured patients with metastatic cancer, applying an expanded definition of palliative care services based on claims data. METHODS: Using nationally representative commercial insurance claims data, we identified patients with metastatic breast, colorectal, lung, bronchus, trachea, ovarian, esophageal, pancreatic, and liver cancers and melanoma between 2001 and 2016. We assessed the annual proportions of these patients who received services specified as, or indicative of, palliative care. Using Cox proportional hazard models, we assessed whether the time from diagnosis of metastatic cancer to first encounter of palliative care differed by demographic characteristics, socioeconomic factors, or region. RESULTS: In 2016, 36% of patients with very poor prognosis cancers received a service specified as, or indicative of, palliative care versus 18% of those with poor prognosis cancers. Being diagnosed in more recent years (2009-2016 v 2001-2008: hazard ratio [HR], 1.8; P < .001); a diagnosis of metastatic esophagus, liver, lung, or pancreatic cancer, or melanoma (v breast cancer, eg, esophagus HR, 1.89; P < .001); a greater number of comorbidities (American Hospital Formulary Service classes > 10 v 0: HR, 1.71; P < .001); and living in the Northeast (HR, 1.43; P < .001) or Midwest (v South: HR, 1.39; P < .001) were the strongest predictors of shorter time from diagnosis to palliative care. CONCLUSION: Use of palliative care among commercially insured patients with advanced cancers has increased since 2001. However, even with an expanded definition of services specified as, or indicative of, palliative care, < 40% of patients with advanced cancers received palliative care in 2016.

Intensity of End-of-Life Care in a Cohort of Commercially Insured Women With Metastatic Breast Cancer in the United States.

PURPOSE: There is limited evidence on the intensity of end-of-life (EOL) care for women < 65 years old, who account for about 40% of breast cancer deaths in the United States. Using established indicators, we estimated the intensity of EOL care among these women. METHODS: We used 2000-2014 claims data from a large US insurer to identify women with metastatic breast cancer who, in the last month of their lives, had more than one hospital admission, emergency department visit, or an intensive care unit (ICU) admission and/or used antineoplastic therapy in the last 14 days of life. Using multivariate logistic regression, we assessed whether intensity of EOL care differed by demographic characteristics, socioeconomic factors, or regions. RESULTS: Adjusted estimates show an increase in EOL ICU admissions between 2000-2003 and 2010-2014 from 14% (95% CI, 10% to 17%) to 23% (95% CI, 20% to 26%) and a small increase in emergency department visits from 10% (95% CI, 7% to 13%) to 12% (95% CI, 9% to 15%), both statistically significant. There was no statistically significant change in the proportions of women experiencing more than one EOL hospitalization (14% in 2010-2014; 95% CI, 11% to 17%) and of those receiving EOL antineoplastic treatment (24% in 2010-2014; 95% CI, 21% to 27%). Living in predominantly mixed, Hispanic, Black, or Asian neighborhoods correlated with more intense care (odds ratio, 1.39; 95% CI, 1.10 to 1.77 for ICU). CONCLUSION: Consistent with findings in the Medicare population, our results suggest an overall increase in the number of ICU admissions at the EOL over time. They also suggest that patients from non-White neighborhoods receive more intense acute care.

What are the volume and budget needs to provide chemotherapy to all children with acute lymphoblastic leukaemia in Thailand? Development and application of an estimation tool.

OBJECTIVE: Insufficient access to anticancer medicines may contribute to the wide survival differences of children with cancers across the globe. We developed a tool to estimate the volume of medicines and budget requirements to provide chemotherapy to children with acute lymphoblastic leukaemia (ALL). DESIGN: Development and application of an estimation tool. SETTING: Paediatric oncology hospital departments in Thailand. PARTICIPANTS: 318 children aged 0-14 years diagnosed with ALL and 215 children with undiagnosed ALL. INTERVENTIONS: Estimates of volume and budget requirements for administering a full course of chemotherapy for ALL and a further course for children who relapse, according to National Treatment Guidelines. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were the volume (mg) and cost (US$) of medicines needed to treat children with ALL. For medicines whose main indication is paediatric ALL (asparaginase and 6-mercaptopurine), we estimated the difference between volume needed and actual sales in 2017 (secondary outcome). RESULTS: Ten anticancer medicines and four chemoprotective agents are needed for the treatment of paediatric ALL according to the Thai treatment guidelines. Of these 14 medicines, 13 are included in the WHO essential medicines list for children. All are available as generics. We estimated that essential chemotherapy and chemoprotective agents to treat all children diagnosed with ALL in Thailand in 2017 would cost US$ 814 952 (US$ 1 365 422 for diagnosed and undiagnosed children), which corresponds to 0.005% (0.008%) of the country's total health expenditure. The volumes of asparaginase and 6-mercaptopurine available on the Thai market in 2017 were more than sufficient (2.3 and 1.5 times the amounts needed, respectively) to treat all children diagnosed with ALL. CONCLUSIONS: Procuring sufficient quantities of essential medicines to treat children with ALL requires relatively modest resources. Medicine cost should not be a major barrier to ALL treatment in similar settings.

Sales of anti-cancer medicines; China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand.

OBJECTIVE: To assess sales of anti-cancer medicines in the 2017 World Health Organization's WHO Model list of essential medicines in China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand from 2007 (2008 for Kazakhstan and Malaysia) to 2017. METHODS: We extracted sales volume data for 39 anti-cancer medicines from the IQVIA database. We divided the total quantity sold by the reference defined daily dose to estimate the total number of defined daily doses sold, per country per year, for three types of anti-cancer therapies (traditional chemotherapy, targeted therapy and endocrine therapy). We adjusted these data by the number of new cancer cases in each country for each year. FINDINGS: We observed an increase in sales across all types of anti-cancer therapies in all countries. The largest number of defined daily doses of traditional chemotherapy per new cancer case was sold in Thailand; however, the largest relative increase per new cancer case occurred in Indonesia (9.48-fold). The largest absolute and relative increases in sales of defined daily doses of targeted therapies per new cancer case occurred in Kazakhstan. Malaysia sold the largest number of adjusted defined daily doses of endocrine therapies in 2017, while China and Indonesia more than doubled their adjusted sales volumes between 2007 and 2017. CONCLUSION: The use of sales data can fill an important knowledge gap in the use of anti-cancer medicines, particularly during periods of insurance coverage expansion. Combined with other data, sales volume data can help to monitor efforts to improve equitable access to essential medicines.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimize the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Time to Entry for New Cancer Medicines: From European Union-Wide Marketing Authorization to Patient Access in Belgium, Estonia, Scotland, and Sweden.

OBJECTIVES: First, to quantify the median time from European Union (EU)-wide approval to first use (launch) for a sample of cancer medicines and number of launches in Belgium, Estonia, Scotland, and Sweden as of June 2015. Second, to assess whether longer times to launch or lack of launches affected medicines with high or low expected additional clinical benefit. Third, to identify possible determinants of the probability of a cancer medicine to be launched. METHODS: Correlation between time to launch and a set of variables hypothesized to affect launch was tested using a complementary log-log model for a sample of 46 cancer medicines that obtained EU-wide marketing authorization between 2000 and 2014. RESULTS: In median, for a sample of 24 cancer medicines that obtained marketing authorization between 2010 and 2014, the expected time from EU-wide marketing authorization to first use of a medicine was shortest in Sweden, 3.1 months, followed by Scotland (9.3 months), Belgium (14.8 months), and Estonia (27.8 months). Median times to launch were longer for the entire sample of 46 cancer medicines that obtained marketing authorization between 2000 and 2014. In the all-country model, medicines with shorter times to submission for reimbursement, local manufacturers headquarter (or local sales representative), and a Food and Drugs Administration priority review or a combination of expedited approval programs and medicines launched in Scotland and Sweden were associated with a higher hazard of launch. Longer times since EU-wide approval initially correlate with an increased hazard but as time further elapses they negatively affect the hazard of launch. CONCLUSIONS: Median times from marketing authorization to first use of cancer medicines were shorter for medicines launched between 2010 and 2014 versus sample-wide (2000-2014). In Estonia, more medicines than in the other countries were not yet launched at the end of the observation period. There was no correlation between Prescrire and European School of Medical Oncology Magnitude of Clinical Benefit Scale ratings of added clinical value and time to launch.

The Implementation of Managed Entry Agreements in Central and Eastern Europe: Findings and Implications.

BACKGROUND: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. METHOD: We conducted a survey on the implementation of MEAs in CEE between January and March 2017. RESULTS: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n = 495, 73%), followed by paybacks (n = 92, 14%), price-volume agreements (n = 37, 5%), free doses (n = 25, 4%), bundle and other agreements (n = 19, 3%), and payment by result (n = 10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the Anatomical Therapeutic Chemical (ATC)-L group, antineoplastic and immunomodulating agents (n = 201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n = 87, 13%), followed by medicines for neurological conditions (n = 83, 13%). CONCLUSIONS: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether, within publicly funded health systems, confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Furthermore, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance, as well as the burden of implementation.

Determinants of utilisation differences for cancer medicines in Belgium, Scotland and Sweden.

BACKGROUND: Little comparative evidence is available on utilisation of cancer medicines in different countries and its determinants. The aim of this study was to develop a statistical model to test the correlation between utilisation and possible determinants in selected European countries. METHODS: A sample of 31 medicines for cancer treatment that obtained EU-wide marketing authorisation between 2000 and 2012 was selected. Annual data on medicines' utilisation covering the in- and out-patient public sectors were obtained from national authorities between 2008 and 2013. Possible determinants of utilisation were extracted from HTA reports and complemented by contacts with key informants. A longitudinal mixed effect model was fitted to test possible determinants of medicines utilisation in Belgium, Scotland and Sweden. RESULTS: In the all-country model, the number of indications reimbursed positively correlated with increased consumption of medicines [one indication 2.6, 95% CI (1.8-3.6); two indications 2.4, 95% CI (1.4-4.3); three indications 4.9, 95% CI (2.2-10.9); all P < 0.01], years since EU-wide marketing authorisation [1.2, 95% CI (1.02-1.4); p < 0.05], price per DDD [0.9, 95% CI (0.998-0.999), P < 0.01], and Prescrire rating [0.5, 95% CI (0.3-0.9), P < 0.05] after adjusting for time and other covariates. CONCLUSIONS: In this study, the most important correlates of increased utilisation in a sample of cancer medicines introduced in the past 15 years were: medicines coverage and time since marketing authorisation. Prices had a negative effect on consumption in Belgium and Sweden. The positive impact of financial MEAs in Scotland suggests that the latter may remove the regressive effect of list prices on consumption.

Progress in increasing affordability of medicines for non-communicable diseases since the introduction of mandatory health insurance in the Republic of Moldova.

BACKGROUND: To assess progress in improving affordability of medicines since the introduction of mandatory health insurance in the Republic of Moldova. METHOD: Using data from national health insurance, we estimate affordability of partially reimbursed medicines for the treatment of non-communicable diseases, and analyse which factors contributed to changes in affordability. RESULTS: Affordability of subsidized medicines improved over time. In 2013, it took a median of 0.84 days of income for the lowest income quintile (ranging from 0 to 3.32 days) to purchase 1 month of treatment for cardiovascular conditions in comparison to 1.85 days in 2006. This improvement however was mainly driven by higher incomes rather than deeper coverage through the reimbursement list. CONCLUSION: If mandatory health insurance is to improve affordability of medicines for the Moldovan population, more funds need to be (re-)allocated to enable higher percentage coverage of essential medicines and efficiencies need to be generated within the health system. These should include a budget reallocation between secondary and primary care, strengthening primary care to manage chronic conditions and raise population awareness, implementation of evidence-based selection and quality use of medicines in both outpatient and inpatient settings, improving monitoring and regulation of prices and the supply chain; and alignment of national treatment guidelines and clinical practice with international best practices and evidence-based medicine.

Dealing with uncertainty and high prices of new medicines: a comparative analysis of the use of managed entry agreements in Belgium, England, the Netherlands and Sweden.

Managed entry agreements are a set of instruments used to reduce the impact of uncertainty and high prices when introducing new medicines. This study develops a conceptual framework for these agreements and tests it by exploring variations in their implementation in Belgium, England, the Netherlands and Sweden and over time as well as their governance structures. Using publicly available data from HTA agencies and survey data from the European Medicines Information Network, a database of agreements implemented between 2003 and 2012 was developed. A review of governance structures was also undertaken. In December 2012 there were 133 active MEAs for different medicine-indications across the four countries. These corresponded to 110 unique medicine-indications. Over time there has been a steady growth in the number of agreements implemented, with the highest number in the Netherlands in 2012. The number of new agreements introduced each year followed a different pattern. In Belgium and England it increased over time, while it decreased in the Netherlands and fluctuated in Sweden. Only 18 (16%) of the unique medicine-indication pairs identified were part of an agreement in two or more countries. England uses mainly discounts and free doses to influence prices. The Netherlands and Sweden have focused more on addressing uncertainties through coverage with evidence development and, in Sweden, on monitoring use and compliance with restrictions through registries. Belgium uses a combination of the above. Despite similar reasons being cited for managed entry agreements implementation, only in a minority of cases have countries implemented an agreement for the same medicine-indication; when they do, a different agreement type is often implemented. Differences in governance across countries partly explain such variations. However, more research is needed to understand whether e.g. risk-perception and/or notion of what constitutes a high price differ between these countries.